It is the long-term objective of the proposed research to determine the electrical parameters required to prevent and reverse the loss of bone mass that occurs in osteoporosis. The sciatic neurectomized rat tibia will be continued to be used to complete the search for an optimal capacitively coupled electrical signal required to reverse an existing denervation disuse osteoporosis. The castrated rat vertebrae will be used as a hormone deficiency osteoporosis. In both osteoporosis models, various electrical signals will be evaluated as to their ability to reverse bone mass loss as determined by wet, dry, and ash weights and mechanical testing. The electrical field and current density induced in the rat tibia and vertebral body will be calculated such that the stage will be set to translate these findings into clinical application of the use of capacitive coupling in treating/preventing osteoporosis in the human. The proposed research will determine the dose-response characteristics of various capacitively coupled fields and various mechanical stresses on isolated bone cell 3H-thymidine, 35S, and 14C-proline incorporation, on cAMP and prostaglandin E2 synthesis, and on calcium flux into and out of the cell as determined by Quin-2, an intracellular calcium indicator. Indomethacin, a prostaglandin synthesis inhibitor, and verapamil, an agent which blocks membrane calcium channels dependent upon membrane depolarization, will be used to try to identify possible mechanisms of action of electrical and mechanical perturbations of isolated bone cells.